Thyrotropin-releasing hormone metabolism in visceral organ homogenates of the rat.
TRH, which is found in a number of sites outside the central nervous system, is degraded by serum and homogenates of brain, liver, and kidney. The presence of TRH deamidase activity in the brain is well documented. In view of the widespread distribution of TRH, the present study was undertaken to evaluate whether TRH deamidase activity is present in visceral organs and to determine the extent to which TRH degradation, as observed under broken cell conditions, can be accounted for by deamidation. Organs from Sprague-Dawley rats were homogenized in 150 mM sodium maleate, pH 7, and aliquots of the 700 X g supernatant were incubated separately with equimolar amounts of synthetic TRH or the deamidated form of TRH, pGlu-His-Pro. The amount of peptide remaining and the conversion of TRH to deamindated TRH in tubes incubated with TRH were measured by specific RIAs at multiple time points. TRH deamidase activity was found in rat liver, kidney, heart, lung, pancreas, ileum, and skeletal muscle. It was time and temperature dependent and was not observed in boiled tissues. Under relative high substrate conditions, approximately 56%, 50%, and 24% of TRH degradation was via the TRH deamidase pathway in liver, kidney, and lung, respectively. In other tissues, the presence of nondeamidase pathways, in addition to the deamidase pathway, could not be ruled out. TRH deamidation accounted for little or no TRH degradation in serum.
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D013973:Thyrotropin-Releasing Hormone; D000581:Amidohydrolases; C019579:TRH deamidase